Common mechanism of pathogenesis in various types of metastatic osteosarcoma.

Abstract

The present study aimed to investigate the common metastatic mechanism in various types of metastatic osteosarcoma (OS). Gene expression profiles generated from the metastatic OS KHOS and KRIB cell lines and the non-metastatic OS HOS cell line were compared. Two groups of differentially expressed genes (DEGs) between KHOS or KRIB and HOS were screened (P<0.01 and |fold change| ≥2) and then underwent Gene Ontology (GO) and pathway enrichment analyses. Subsequently, the protein-protein interaction (PPI) network was constructed and the subnetwork was mined. Furthermore, overlapping DEGs of these two groups were identified and pathway enrichment and regulatory network analyses were performed. A total of 1,552 and 1,330 DEGs from KHOS vs. HOS and KRIB vs. HOS were obtained, respectively. GO and pathway enrichment analyses of DEGs between KRIB and HOS, including anatomical structure morphogenesis and focal adhesion, were similar to those between KHOS and HOS. Vascular endothelial growth factor A and epidermal growth factor receptor were hub nodes in the PPI network for KHOS and KRIB. Subnetworks of these two groups were similar. In addition, 421 upregulated and 595 downregulated overlapping genes were enriched in the mitogen-activated protein kinase and transforming growth factor-β signaling pathways. Furthermore, seven vital transcription factors, including hes-related family bHLH transcription factor with YRPW motif 1 (HEY1), were obtained. Overall, different types of metastatic OS were shown to exhibit a similar mechanism of pathogenesis. With the exception of cell adhesion and angiogenesis, recapitulation of the morphogenetic processes facilitates OS tumor formation and metastasis. Genes such as HEY1 are important for metastatic OS. Further studies are required in order to confirm these results.